Spitz nevus with EHBP1‐ALK fusion and distinctive membranous localization of ALK

Abstract

ALK rearrangements define a histopathologically distinctive yet diverse subset of Spitz tumors characterized by fusiform to epithelioid melanocytes with frequent fascicular growth and ALK overexpression. Molecularly, these tumors are characterized by fusions between ALK and a variety of gene partners, most commonly TPM3 and DCTN1. We describe an unusual case of a Spitz nevus occurring in a 13‐year‐old female that manifested ALK immunopositivity with cell membrane localization. The proliferation was polypoid and composed of elongated nests of epithelioid melanocytes with enlarged nuclei, prominent nucleoli, and abundant cytoplasm without significant atypia and lacking mitotic figures. The nevus exhibited strong and diffuse expression of p16. Targeted next‐generation RNA sequencing revealed an in‐frame EHBP1‐ALK fusion, which has been reported only once in the literature. EHBP1 encodes an adaptor protein with plasma membrane targeting potential. Together, these findings suggest that the 5′ ALK fusion partner in Spitz tumors may dictate the subcellular localization of the ALK chimeric oncoprotein. In summary, this case highlights a rare ALK fusion associated with a distinct immunohistochemical staining pattern and further expands the spectrum of ALK‐rearranged melanocytic tumors.

Kinase Fusions in Spitz Melanocytic Tumors: The Past, the Present, and the Future

“…This work showed that the prevalence of ALK rearrangement was rather frequent when certain morphological features were present. Finally, it is important to emphasize that in some papers, the ALK immunostaining pattern is described as membranous with different types of fusion genes [15].…”

Spitz melanocytic neoplasms with MLPH::ALK fusions: Report of two cases with previously unreported features and literature review

“…Other less frequent fusion partners include NPM1 , TPR , CLIP1 , GTF3C2 , MLPH , EEF2 , MYO5A , and KANK1 8–12 . Most recently, EHBP1 has also been reported as the fusion partner of ALK in a pediatric patient with SN 13 …”

“…[8][9][10][11][12] Most recently, EHBP1 has also been reported as the fusion partner of ALK in a pediatric patient with SN. 13 To date, only a handful of documented instances of Spitz tumors featuring MLPH::ALK fusions have been noted within the English literature, highlighting their exceptional scarcity. [10][11][12] Herein, we present two additional cases of Spitz melanocytic neoplasms with MLPH::ALK fusions, including a previously unreported Spitz melanoma.…”